Adenosine, produced from the metabolism of adenosine triphosphate (ATP), mediates a number of physiological actions by targeting G protein-coupled receptors, termed adenosine receptors (ARs). Four distinct types of these receptors, namely the A1, A2A, A2B and A3AR, have been identified and cloned, each of which shows distinct tissue distribution and function. A number of these receptors are targeted by caffeine and theophylline, ingredients in coffee and tea, which block the effects of endogenous adenosine at these receptor sites and provide the stimulant properties of these beverages. In recent years, a number of laboratories have been studying the role of these receptors in cancers. A number of studies have demonstrated that activation of ARs can either increase or decrease cancer cell proliferation and metastasis. This review will provide evidence implicating ARs in regulating cancer cell growth and proliferation and show how agonists or antagonists for these receptors could mediate anti-cancer responses. The cell signaling pathways mediating the differential responses to activation of AR subtypes will also be discussed.
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